Response differences among mouse strains in DNA damage and skin carcinogenicity of 7,12-dimethylbenz[a]anthracene are due to inducible aryl hydrocarbon hydroxylase activity.
Strain differences of mice in the induction of DNA damage in peripheral blood cells and skin tumors were investigated using 7,12-dimethylbenz[a]anthracene (DMBA). DMBA-induced DNA damage and skin tumorigenesis were evaluated using the single cell gel electrophoresis (SCGE) assay and 2-stage carcinogenicity study, respectively. DNA damaged cells were markedly increased in the aryl hydrocarbon hydroxylase (AHH)-inducible mice, BALB/c and C57BL/6, as compared with the AHH-noninducible mice, DBA/2, in the SCGE assay. The AHH-inducible mice were more sensitive to DMBA than the AHH-noninducible mice in the 2-stage carcinogenicity study. These results strongly suggest that the genetic capacity to metabolize PAH is associated with the mutagenicity and carcinogenicity of DMBA.
Sato
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Toxicology Research Laboratories, Japan Tobacco Inc., Hatano-shi.
Tomita
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D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D002273:Carcinogens / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004586:Electrophoresis; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000235:genetics; D013045:Species Specificity
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D001189:Aryl Hydrocarbon Hydroxylases